Asymmetric reduction of prochiral ketones produces optically active alcohols. In view of the importance of such reductions, considerable effort has been expended in finding asymmetric reducing agents which will achieve reduction of such carbonyl groups to give optically active alcohols of high optical purity.
The first successful preparation of an efficient chiral organoborane reducing agent was achieved by Professor Mark Midland (See Midland, M. M.; Tramontano, A.; Zderic, S. A. J. Am. Chem. Soc. 1979, 101, 2352) who synthesized B-isopinocampheyl-9-borabicyclo[3.3.1]nonane (sold by Aldrich Chemical Company, Inc., Milwaukee, Wis. under the trademark Alpine-Borane.RTM.). This reagent is very efficient in reducing reactive carbonyl groups such as .alpha.-deuteraldehydes, .alpha.,.beta.-acetylenic ketones, .alpha.-keto esters and .alpha.-halo ketones. However, chiral reduction of slower reacting ketones such as aralkyl and dialkyl ketones were not successful.
To overcome these deficiencies, B-chlorodiisopinocampheylborane (Ipc.sub.2 BCl) (sold by Aldrich Chemical Company, Inc., Milwaukee, Wis. under the trademark DIP-Chloride.RTM.) was developed. B-chlorodiisopinocampheylborane reacts with ketones at a considerably faster rate than the Alpine-Borane reagent (Brown, H. C.; Chandrasekharan, J; Ramachandran, P. V. J., J. Am. Chem. Soc. 1988, 110, 1539). Ipc.sub.2 BCl is an excellent reagent for the reduction of prochiral aralkyl ketones and provides essentially optically pure product alcohols for most types of aralkyl ketones. It is also highly effective for reducing .alpha.-quaternary alkyl ketones. The success of reduction of such ketones with Ipc.sub.2 BCl may be explained by a tentative mechanism where the .alpha.-quaternary alkyl group has to sterically interact with the methyl group at the 2-position of the isopinocampheyl moiety. However, when the steric interaction between the reagent and the ketone is less as is the case of the reduction of 3-methyl-2-butanone (32% ee) and 2-butanone (4% ee), the chiral induction is poor.
It remains highly desirable to develop a reagent which will reduce a broad spectrum of ketones. The present invention provides B-halodiiso-2-ethylapopinocampheylboranes which fulfill that need.
One of the compounds of this invention was reported by Jadhav., P. K.; Bhat, K. S.; Perumal, P. T.; Brown, H. C., J. Org. Chem. 1986, 51, 432, bis(10-methylisopinocampheyl)chloroborane. The compound was only of 92% ee and 92% chemical purity which is not sufficient for use in chiral reductions. The compounds of this invention are chemically and optically pure.